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In late 2019, the emergence of a novel coronavirus led to its identification as SARS-CoV-2, precipitating the onset of the COVID-19 pandemic. Many experimental and computational studies were performed on SARS-CoV-2 to understand its behavior and patterns. In this research, Molecular Dynamic (MD) simulation is utilized to compare the behaviors of SARS-CoV-2 and its Variants of Concern (VOC)-Alpha, Beta, Gamma, Delta, and Omicron-with the hACE2 protein. Protein structures from the Protein Data Bank (PDB) were aligned and trimmed for consistency using Chimera, focusing on the receptor-binding domain (RBD) responsible for ACE2 interaction. MD simulations were performed using Visual Molecular Dynamics (VMD) and Nanoscale Molecular Dynamics (NAMD2), and salt bridges and hydrogen bond data were extracted from the results of these simulations. The data extracted from the last 5 ns of the 10 ns simulations were visualized, providing insights into the comparative stability of each variant's interaction with ACE2. Moreover, electrostatics and hydrophobic protein surfaces were calculated, visualized, and analyzed. Our comprehensive computational results are helpful for drug discovery and future vaccine designs as they provide information regarding the vital amino acids in protein-protein interactions (PPIs). Our analysis reveals that the Original and Omicron variants are the two most structurally similar proteins. The Gamma variant forms the strongest interaction with hACE2 through hydrogen bonds, while Alpha and Delta form the most stable salt bridges; the Omicron is dominated by positive potential in the binding site, which makes it easy to attract the hACE2 receptor; meanwhile, the Original, Beta, Delta, and Omicron variants show varying levels of interaction stability through both hydrogen bonds and salt bridges, indicating that targeted therapeutic agents can disrupt these critical interactions to prevent SARS-CoV-2 infection.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Simulação de Dinâmica Molecular , Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Humanos , COVID-19/virologia , COVID-19/metabolismo , Ligação de Hidrogênio , Sítios de LigaçãoRESUMO
Ciprofloxacin-resistant Salmonella Typhimurium (S. Typhimurium) causes a significant health burden worldwide. A wealth of studies has been published on the contributions of different mechanisms to ciprofloxacin resistance in Salmonella spp. But we still lack a deep understanding of the physiological responses and genetic changes that underlie ciprofloxacin exposure. This study aims to know how phenotypic and genotypic characteristics are impacted by ciprofloxacin exposure, from ciprofloxacin-susceptible to ciprofloxacin-resistant strains in vitro. Here, we investigated the multistep evolution of resistance in replicate populations of S. Typhimurium during 24 days of continuously increasing ciprofloxacin exposure and assessed how ciprofloxacin impacts physiology and genetics. Numerous studies have demonstrated that RamA is a global transcriptional regulator that prominently perturbs the transcriptional landscape of S. Typhimurium, resulting in a ciprofloxacin-resistant phenotype appearing first; the quinolone resistance-determining region mutation site can only be detected later. Comparing the microbial physiological changes and RNA sequencing (RNA-Seq) results of ancestral and selectable mutant strains, the selectable mutant strains had some fitness costs, such as decreased virulence, an increase of biofilm-forming ability, a change of "collateral" sensitivity to other drugs, and inability to utilize galactitol. Importantly, in the ciprofloxacin induced, RamA directly binds and activates the gatR gene responsible for the utilization of galactitol, but RamA deletion strains could not activate gatR. The elevated levels of RamA, which inhibit the galactitol metabolic pathway through the activation of gatR, can lead to a reduction in the growth rate, adhesion, and colonization resistance of S. Typhimurium. This finding is supported by studies conducted in M9 medium as well as in vivo infection models. IMPORTANCE: Treatment of antibiotic resistance can significantly benefit from a deeper understanding of the interactions between drugs and genetics. The physiological responses and genetic mechanisms in antibiotic-exposed bacteria are not well understood. Traditional resistance studies, often retrospective, fail to capture the entire resistance development process and typically exhibit unpredictable dynamics. To explore how clinical isolates of S. Typhimurium respond to ciprofloxacin, we analyzed their adaptive responses. We found that S. Typhimurium RamA-mediated regulation disrupts microbial metabolism under ciprofloxacin exposure, affecting genes in the galactitol metabolic pathways. This disruption facilitates adaptive responses to drug therapy and enhances the efficiency of intracellular survival. A more comprehensive and integrated understanding of these physiological and genetic changes is crucial for improving treatment outcomes.
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Antibacterianos , Ciprofloxacina , Farmacorresistência Bacteriana , Regulação Bacteriana da Expressão Gênica , Salmonella typhimurium , Ciprofloxacina/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Virulência , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Animais , Camundongos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , MutaçãoRESUMO
DNA damage is a critical factor contributing to genetic alterations, directly affecting human health, including developing diseases such as cancer and age-related disorders. DNA repair mechanisms play a pivotal role in safeguarding genetic integrity and preventing the onset of these ailments. Over the past decade, substantial progress and pivotal discoveries have been achieved in DNA damage and repair. This comprehensive review paper consolidates research efforts, focusing on DNA repair mechanisms, computational research methods, and associated databases. Our work is a valuable resource for scientists and researchers engaged in computational DNA research, offering the latest insights into DNA-related proteins, diseases, and cutting-edge methodologies. The review addresses key questions, including the major types of DNA damage, common DNA repair mechanisms, the availability of reliable databases for DNA damage and associated diseases, and the predominant computational research methods for enzymes involved in DNA damage and repair.
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Human milk is the best source of nutrition for infants. Lower freezing temperatures and faster freezing rates allow for better preservation of human milk. However, research on the freezing conditions of human milk is limited. This study investigated the effectiveness of quick freezing and suitable freezing conditions for home preservation. Human milk was stored under different freezing conditions (-18 °C, -18 °C quick freezing, -30 °C, -40 °C, -60 °C, and - 80 °C) for 30, 60, and 90 days and then evaluated for changes in the microbial counts, bioactive protein, and lipid. The results showed that the total aerobic bacterial and Bifidobacteria counts in human milk after storage at freezing temperatures of - 30 °C and lower were closer to those of fresh human milk compared to - 18 °C. Furthermore, the lysozyme loss, lipid hydrolysis degree, and volatile organic compound production were lower. However, -18 °C quick freezing storage was not markedly different from -18 °C in maintaining human milk quality. Based on the results, for household and environmental reasons, the recommended temperature for storing human milk is suggested as -30 °C.
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Temperatura Baixa , Leite Humano , Humanos , Congelamento , Leite Humano/microbiologia , Refrigeração , LipídeosRESUMO
Riemerella anatipestifer (R. anatipestifer) is a multidrug-resistant bacterium and an important pathogen responsible for major economic losses in the duck industry. Our previous study revealed that the efflux pump is an important resistance mechanism of R. anatipestifer. Bioinformatics analysis indicated that the GE296_RS02355 gene (denoted here as RanQ), a putative small multidrug resistance (SMR)-type efflux pump, is highly conserved in R. anatipestifer strains and important for the multidrug resistance. In the present study, we characterized the GE296_RS02355 gene in R. anatipestifer strain LZ-01. First, the deletion strain RA-LZ01ΔGE296_RS02355 and complemented strain RA-LZ01cΔGE296_RS02355 were constructed. When compared with that of the wild-type (WT) strain RA-LZ01, the mutant strain ΔRanQ showed no significant influence on bacterial growth, virulence, invasion and adhesion, morphology biofilm formation ability, and glucose metabolism. In addition, the ΔRanQ mutant strain did not alter the drug resistance phenotype of the WT strain RA-LZ01 and displayed enhanced sensitivity toward structurally related quaternary ammonium compounds, such as benzalkonium chloride and methyl viologen, which show high efflux specificity and selectivity. This study may help elucidate the unprecedented biological functions of the SMR-type efflux pump in R. anatipestifer. Thus, if this determinant is horizontally transferred, it could cause the spread of quaternary ammonium compound resistance among bacterial species.
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Colistin (polymyxin E) is a group of cationic antimicrobial cyclic peptides and is recognized as a last-resort defense against lethal infections with carbapenem-resistant pathogens. In addition to the plasmid-borne mobilized phosphoethanolamine (PEA) transferases, the functional expression of lipid A-modifying enzymes encoded on chromosomes has been attributed to intrinsic bacterial colistin resistance. However, the mechanisms of colistin resistance in Riemerella anatipestifer remain unknown. Herein, the GE296_RS09715 gene-encoded Lipid A PEA transferases (RaEptA) was identified in R. anatipestifer. Genetic and structural analyses revealed that the amino acid sequence of RaEptA shared 26.6%-33.1% similarities with the family of Lipid A PEA transferases (EptA) and MCR-like proteins and have defined 12 residues that contribute to the formation of phosphatidylethanolamine (PE)-recognizable cavities. Comparative analyses of colistin resistance in RA-LZ01 and RA-LZ01ΔRaEptA showed the level of colistin has fallen from 96 µg mL-1 down to 24 ~ 32 µg mL-1 . Site-directed mutagenesis assay of the PE-binding cavity and expression of the mutants reveals that K309-rRaEptA can remodel the surface of Escherichia coli and rendering it resistant to colistin, suggesting this point-mutation of P309K is necessary for EptA-mediated lipid A modification. Moreover, the virulence of RA-LZ01ΔRaEptA was attenuated compared with RA-LZ01 both in vivo and vitro. Taken together, the results represent the RaEptA involved in the colistin resistance and pathogenicity, and the P309K mutation might alter bacterial adaptation and increase the spread of colistin resistance from R. anatipestifer to other gram-negative bacteria. The findings of this study suggest another scenario for the spread of colistin resistance genes and should be considered by a wide audience.
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Antibacterianos , Colistina , Colistina/farmacologia , Colistina/química , Antibacterianos/farmacologia , Virulência/genética , Lipídeo A/química , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Fenótipo , TransferasesRESUMO
There is no doubt that antimicrobial resistance (AMR) is a global threat to public health and safety, regardless of whether it's caused by people or natural transmission. This study aimed to investigate the genetic characteristics and variations of tigecycline-resistant Gram-negative isolates from herbivores in northwest China. In this study, a total of 300 samples were collected from various provinces in northwest China, and 11 strains (3.67%) of tigecycline-resistant bacteria were obtained. In addition, bacterial identification and antibiotic susceptibility testing against 14 antibiotics were performed. All isolates were multiple drug-resistant (MDR) and resistant to more than three kinds of antibiotics. Using an Illumina MiSeq platform, 11 tigecycline-resistant isolates were sequenced using whole genome sequencing (WGS). The assembled draft genomes were annotated, and then sequences were blasted against the AMR gene database and virulence factor database. Several resistance genes mediating drug resistance were detected by WGS, including fluoroquinolone resistance genes (gyrA_S83L, gyrA_D87N, S83L, parC_S80I, and gyrB_S463A), fosfomycin resistance genes (GlpT_E448K and UhpT_E350Q), beta-lactam resistance genes (FtsI_D350N and S357N), and the tigecycline resistance gene (tetR N/A). Furthermore, there were five kinds of chromosomally encoded genetic systems that confer MDR (MarR_Y137H, G103S, MarR_N/A, SoxR_N/A, SoxS_N/A, AcrR N/A, and MexZ_K127E). A comprehensive analysis of MDR strains derived from WGS was used to detect variable antimicrobial resistance genes and their precise mechanisms of resistance. In addition, we found a novel ST type of Escherichia coli (ST13667) and a newly discovered point mutation (K127E) in the MexZ gene of Pseudomonas aeruginosa. WGS plays a crucial role in AMR control, prevention strategies, as well as multifaceted intervention strategies.
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The hydrophilicity and inherent flammability of cotton textiles severely limit their usage. To solve these drawbacks, a superhydrophobic and flame-retardant (SFR) coating made of chitosan (CH), ammonium polyphosphate (APP), and TiO2-SiO2-HMDS composite was applied to cotton fabric using simple layer-by-layer assembly and dip-coating procedures. First, the fabric was alternately immersed in CH and APP water dispersions, and then immersed in TiO2-SiO2-HMDS composite to form a CH/APP@TiO2-SiO2-HMDS coating on the cotton fabric surface. SEM, EDS, and FTIR were used to analyze the surface morphology, element composition, and functional groups of the cotton fabric, respectively. Vertical burning tests, microscale combustion calorimeter tests, and thermogravimetric analyses were used to evaluate the flammability, combustion behavior, thermal degradation characteristics, and flame-retardant mechanism of this system. When compared to the pristine cotton sample, the deposition of CH and APP enhanced the flame retardancy, residual char, heat release rate, and total heat release of the cotton textiles. The superhydrophobic test results showed that the maximal contact angle of SFR cotton fabric was 153.7°, and possessed excellent superhydrophobicity. Meanwhile, the superhydrophobicity is not lost after 10 laundering cycles or 50 friction cycles. In addition, the UPF value of CH/APP@TiO2-SiO2-HMDS cotton was 825.81, demonstrating excellent UV-shielding properties. Such a durable SFR fabric with a facile fabrication process exhibits potential applications for both oil/water separation and flame retardancy.
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Gases such as hydrogen sulfide, nitric oxide and sulfur dioxide have important regulatory effects on the endocrine and physiological processes of the body and are collectively referred to as "gas signaling molecules". These gas signaling molecules are also closely related to Alzheimer's disease, the inflammatory response and depression. In this paper, we introduce the production and metabolic pathways of NO, H2S and SO2 in living organisms and review the regulatory functions of gas signaling molecules in the endocrine system and their mechanisms in relation to their clinical applications. This work will provide a basis for finding targets for intervention and establishing novel prevention and treatment strategies for related diseases.
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Sulfeto de Hidrogênio , Transdução de Sinais , Humanos , Transdução de Sinais/fisiologia , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Dióxido de EnxofreRESUMO
Promoting processing efficiency and taking advantage of agricultural by-products are two promising ways to achieve sustainable textile industry. This study presents a customized efficient ultrasonic-assisted bleaching strategy for yak hair - a widely existing but underexploited secondary dark shade fibre from yak. A melanin-targeted Fenton oxidation process is established which involves three phases, i.e., (I) incorporation of Fe2+ ions with melanin, (II) catalytic oxidative bleaching using hydrogen peroxide (H2O2), and (III) reductive cleansing. The bleaching efficacy, dyeing performance and tensile property of yak hair treated with and without ultrasound were explored and compared. Further, the ultrasonic bleaching mechanism in terms of the catalytic effect of Fe2+ ions, the promotion of H2O2 decomposition, removal of melanin granule from yak hair, were demonstrated. Finally, the main effects and interactions of parameters in phase II, and optimal condition were obtained through mathematical modelling based on a central composite design (CCD). Results reveal that ultrasonic bleaching dramatically enhances the whiteness index (WI) of yak hair from 11 to 45 which is 44.6% higher than those bleached without ultrasound, and also promotes the uptake of acid dyes. There is only 15% tensile strength loss and 14% elongation increment of yak hair after ultrasonic bleaching, rising from a slight damage of cuticle layer and cleavage of disulfide bonds, respectively. In the study of bleaching mechanism, Fe2+ ion is confirmed to improve the H2O2 decomposition rate by 20.9% which further runs up to 35.9% after introducing ultrasound. Ultrasound increases the concentration of hydroxyl radicals (HO) by 94% which are the main oxidative species participating in bleaching confirmed by HO scavenging experiment. The porous structure was observed on the cross section of yak hair stemming from the removal of melanin granules contributed by the cleaning action of ultrasound. A theoretical highest WI of 52.4 can be achieved under an optimal condition based on the CCD study. In general, the proposed melanin-targeted bleaching strategy for yak hair that integrates ultrasonic technology and Fenton reaction, is beneficial to the development of sustainable textile industry from material and processing perspectives.
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Peróxido de Hidrogênio , Melaninas , Animais , Bovinos , Corantes , Cabelo/química , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Melaninas/análise , Melaninas/metabolismo , Melaninas/farmacologia , Oxirredução , UltrassomRESUMO
To reduce the energy and water consumption from a conventional textile industry, a facile and efficient UVA-assisted scouring/bleaching strategy has been customized for cotton/spandex in this research. The bleaching efficacy under UVA irradiation is explored by comparing diverse processes, i.e., Scouring only (Sc.); Conventional scouring and pad-steam bleaching (Sc/BlConv-PS); Conventional scouring and cold pad-batch bleaching (Sc/BlConv-CPB); and one or two-step scouring and UVA-assisted bleaching (Sc/BlUVA-I, Sc/BlUVA-II). The significance, interactive effect and optimisation of parameters on the whiteness index (WI) of fabric are investigated through mathematical modelling. The bleaching mechanism is analysed by a fluorescence labelling method. The dyeing and tensile properties of fabrics and the energy conservation during processing are also demonstrated. Results show that Sc/BlUVA-I achieves an equivalent scouring and bleaching effect as Sc/BlUVA-II. A superior bleaching effect of Sc/BlUVA-II over that of Sc/BlConv-PS reveals the better function of catalytic UVA than conventional steam. Under the theoretical optimal bleaching conditions (H2O2 conc. 42.96 g L-1, pH 10.24 and irradiation time 3.68 h), a calculated highest WI of 77.19 (1.48 times higher than that of untreated fabric) can be achieved based on the mathematical modelling. Through mechanism studies, hydroxyl radicals are confirmed as the main oxidative species taking part in UVA-assisted bleaching and their concentration in simulated bleaching solution dramatically increases upon the introduction of UVA. The fabric treated by Sc/BlUVA-I exhibits an acceptable strength decrease (<10%) and excellent dyeing performance with reactive dyes. The Sc/BlUVA-I strategy enables more than ca. 70% of energy conservation than the Sc/BlConv-PS process. The encouraging results manifest the practicability and promising prospects of UVA-assisted pre-treatment which contributes to enhancing the sustainability of the textile industry.
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4-Substituted catechols with different C[double bond, length as m-dash]C bonds as urushiol analogues were synthesized through the a three-step route including reductive amination reaction of 3,4-dihydroxybenzaldehyde with N-Boc-piperazine, Boc deprotection, and amidation with various fatty acids. Electrochemical polymerization of these analogues on a copper surface afforded robust coatings with desirable adhesive force, hydrophobicity and thermal stability. Cyclic voltammetry and infrared spectroscopic characterizations revealed that the coating formation of urushiol analogues resulted from the electrooxidation-induced radical coupling of phenoxyl radicals with a phenyl ring and the side chain C[double bond, length as m-dash]C bond. The coating of the urushiol analogue bearing only one side chain C[double bond, length as m-dash]C bond exhibited the best performance in copper corrosion inhibition, with an inhibition efficiency of 99.99% and long-term effect (99.9% after 4 weeks of immersion in 3.5 wt% NaCl). The desired performance of these urushiol analogues suggests that they could be of practical applications as an alternative to the resource-limited natural urushiol.
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Bladder cancer (BC) is among the most common tumors with a high recurrence rate, necessitating noninvasive and sensitive diagnostic methods. Accurate detection of exfoliated tumor cells (ETCs) in urine is crucial for noninvasive BC diagnosis but suffers from limited sensitivity when ETCs are rare and confounded by reactive, regenerative, or reparative cells. Single-cell sequencing (SCS) enables accurate detection of ETCs by surveying oncogenic driver mutations or genome-wide copy number alternations. To overcome the low-throughput limitation of SCS, we report a SCS-validated cellular marker, hexokinase 2 (HK2), for high-throughput screening cells in urine and detecting ETCs engaging elevated glycolysis. In the SCS-based training set, a total of 385 cells from urine samples of eight urothelial carcinoma (UC) patients were sequenced to establish a HK2 threshold that achieved >90% specificity for ETC detection. This urine-based HK2 assay was tested with a blinded patient group (n = 384) including UC and benign genitourinary disorders as a validation cohort for prospectively evaluating diagnostic accuracy. The sensitivity, specificity, positive predictive value, and negative predictive value of the assay were 90, 88, 83, and 93%, respectively, which were superior to urinary cytology. For investigating the potential to be a screening test, the HK2 assay was tested with a group of healthy individuals (n = 846) and a 6-month follow-up. The specificity was 98.4% in this health group. Three participants were found to have >5 putative ETCs that were sequenced to exhibit recurrent copy number alternations characteristic of malignant cells, demonstrating early BC detection before current clinical methods.
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Hexoquinase/genética , Hexoquinase/metabolismo , Programas de Rastreamento , Análise de Célula Única , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Linhagem Celular Tumoral , Humanos , Valor Preditivo dos Testes , Análise de Sequência , Neoplasias da Bexiga Urinária/patologiaRESUMO
This study presents a high-efficient and cost-effective ultrasound-assisted strategy for one-bath one-step scouring and bleaching of cotton/spandex fabric using sodium percarbonate (SPC) and tetraacetylenediamine (TAED) couple. SPC plays both roles of pH regulator and H2O2 donor to initiate the peracetic acid (PAA) release from TAED. The significance and interaction effects of operating parameters (TAED concentration, temperature and time) on the WI (Whiteness Index) of fabrics were investigated through a central composite design. The bleaching mechanism was studied by exploring the relationship between WI and PAA and hydroxyl radical (HO·) concentrations. The mechanical and dyeing performances of treated fabrics were also evaluated. Results show that temperature exerted a significant impact on WI followed by TAED concentration and time. The PAA concentration decreased and HO· concentration increased upon the temperature rise. Both PAA and HO· were significant to upgrade WI and ultrasound was effective in enhancing their bleaching efficiency. The fabric treated only with 15 mmol/L TAED and 10 mmol/L SPC at 40 °C for 40 min under ultrasound could achieve a WI of 68.6 (43% higher than greige fabric), which was almost equivalent to that of the fabric treated at 60 °C without ultrasound. This verifies the contribution of ultrasound technology in reducing bleaching temperature for energy-saving purpose. Moreover, the treated fabric displayed less than 5% tensile strength loss, having a marginal impact on the apparel performance. The wettability of fabric was greatly improved leading to a good dyeing performance. Encouraging results demonstrate the high efficiency of the ultrasound-assisted pre-treatment process of cotton/spandex fabric, which contributes to the sustainable production of textiles.
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Background: Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between Rap1A gene rs494453 polymorphism and HCC. However, the relationship between Rap1A rs494453 polymorphism and HCC recurrence after LT remained unclear. Methods: A total of 74 HCC patients who underwent LT from July 2005 to June 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as Rap1A rs494453. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The Rap1A rs494453 genotype frequencies were determined using the Χ² test and the minor allele frequencies (MAFs) of Rap1A rs494453 genotypes were calculated by Hardy-Weinberg equilibrium. Results: We found that the donor Rap1A rs494453 polymorphism was profoundly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and donor Rap1A rs494453 genotype were proved to be independent risk factors for HCC recurrence. Patients with donor AG/GG genotypes had a distinct lower RFS and OS than AA genotype. The TNM stage, Milan criteria, microvascular invasion, and donor Rap1A rs494453 genotype were independent factors for the RFS of LT patients. Conclusions: Donor Rap1A rs494453 is a potential predictive marker for HCC recurrence risk after LT.
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Wireless sensor network (WSN) nodes are devices with limited power, and rational utilization of node energy and prolonging the network lifetime are the main objectives of the WSN's routing protocol. However, irrational considerations of heterogeneity of node energy will lead to an energy imbalance between nodes in heterogeneous WSNs (HWSNs). Therefore, in this paper, a routing protocol for HWSNs based on the modified grey wolf optimizer (HMGWO) is proposed. First, the protocol selects the appropriate initial clusters by defining different fitness functions for heterogeneous energy nodes; the nodes' fitness values are then calculated and treated as initial weights in the GWO. At the same time, the weights are dynamically updated according to the distance between the wolves and their prey and coefficient vectors to improve the GWO's optimization ability and ensure the selection of the optimal cluster heads (CHs). The experimental results indicate that the network lifecycle of the HMGWO protocol improves by 55.7%, 31.9%, 46.3%, and 27.0%, respectively, compared with the stable election protocol (SEP), distributed energy-efficient clustering algorithm (DEEC), modified SEP (M-SEP), and fitness-value-based improved GWO (FIGWO) protocols. In terms of the power consumption and network throughput, the HMGWO is also superior to other protocols.
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New strategies based on advanced technologies are highly desired for expanding the applications of biological macromolecules in the applied scientific fields. In the present study, a new kind of core-shell nano depots were designed, in which the shell section was a drug-polymer composite and the core section was a drug reservoir. With ethyl cellulose and ketoprofen as a filament-forming polymeric matrix and a model drug, respectively, a triaxial electrospinning apparatus was developed to conduct both coaxial and triaxial processes, by which monolithic nanofibers F1 and core-shell nano depots F2 were successfully prepared. Although both of them had the same double components, their different nanostructures generated considerable differences in providing drug sustained release profiles. The core-shell nanofiber depots F2 were able to provide a better zero-order drug release profile: no initial burst release, smooth sustained release effect, and smaller tailing-off release for a nice zero-order drug release kinetics. The release percentage (Q) can be linearly manipulated through the release time (t) according to the equation Q2 = 9.40 + 4.74 t (R = 0.9936), providing opportunity for precise administration. The developed strategy and advanced electrospinning technique exhibit a new way for constructing process-structure-performance relationships at nano scale and for expanding the potential applications of biological macromolecules in the applied fields.
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Portadores de Fármacos/química , Eletricidade , Fluorocarbonos/química , Nanoestruturas/química , Liberação Controlada de FármacosRESUMO
Lithium metal batteries are promising candidates for next generation high energy batteries. However, an undesirable dendrite growth hinders their practical applications. Herein, a three-dimensional (3D) porous carbon nanotube film decorated with Ag nanoparticles (CNT/Ag) has been synthesized via the thermal decomposition reaction of AgNO3 into Ag nanoparticles, and then is transformed into a 3D porous CNT/Ag/Li film via thermal infusion to obtain a high-performance free-standing lithium host. This as-formed 3D CNT/Ag/Li host can effectively restrain the dendrite growth by guiding Li deposition via the highly lithiophilic Ag nanoparticle seeds and lowering local current density of the highly conductive matrix. The as-prepared CNT/Ag/Li electrode exhibits long-term cycling stability over 200 cycles at a current density of 1 mA cm-2 with an areal capacity of 1.0 mA h cm-2. Moreover, the full cell paired with a sulfur/C cathode shows good cycling stability. Therefore, the 3D porous CNT/Ag/Li film formed via a facile three-step fabrication process can enlarge the cycle lifetime of a lithium metal anode.
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Globally, epithelial ovarian cancer (EOC) is the most common gynecological malignancy with poor prognosis. The expression and oncogenic roles of ubiquitin specific peptidase 5 (USP5) have been reported in several cancers except EOC. In the current study, USP5 amplification was highly prevalent in patients with EOC and associated with higher mRNA expression of USP5. USP5 amplification and overexpression was positively correlated with poor prognosis of patients of ovarian serous carcinomas. Disruption of USP5 profoundly repressed cell proliferation by inducing cell cycle G0/G1 phase arrest in ovarian cancer cells. Additionally, USP5 knockdown inhibited xenograft growth in nude mice. Knockdown of USP5 decreased histone deacetylase 2 (HDAC2) expression and increased p27 (an important cell cycle inhibitor) expression in vitro and in vivo. The promoting effects of USP5 overexpression on cell proliferation and cell cycle transition, as well as the inhibitory effects of USP5 overexpression on p27 expression were mediated by HDAC2. Moreover, USP5 interacted with HDAC2, and disruption of USP5 enhanced the ubiquitination of HDAC2. HDAC2 protein was positively correlated USP5 protein, and negatively correlated with p27 protein in ovarian serous carcinomas tissues. Collectively, our data suggest the oncogenic function of USP5 and the potential regulatory mechanisms in ovarian carcinogenesis.
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Carcinoma Epitelial do Ovário/enzimologia , Carcinoma Epitelial do Ovário/patologia , Endopeptidases/metabolismo , Histona Desacetilase 2/metabolismo , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologia , Idoso , Animais , Carcinógenos/metabolismo , Carcinoma Epitelial do Ovário/genética , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Endopeptidases/genética , Feminino , Amplificação de Genes , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , UbiquitinaçãoRESUMO
Hydra is a small freshwater polyp capable of regeneration from small tissue pieces and from aggregates of cells. During regeneration, a hollow bilayered sphere is formed that undergoes osmotically driven shape oscillations of inflation and rupture. These oscillations are necessary for successful regeneration. Eventually, the oscillating sphere breaks rotational symmetry along the future head-foot axis of the animal. Notably, the shape oscillations show an abrupt shift from large-amplitude, long-period oscillations to small-amplitude, short-period oscillations. It has been widely accepted that this shift in oscillation pattern is linked to symmetry breaking and axis formation, and current theoretical models of Hydra symmetry breaking use this assumption as a model constraint. However, a mechanistic explanation for the shift in oscillation pattern is lacking. Using in vivo manipulation and imaging, we quantified the shape oscillation dynamics and dissected the timing and triggers of the pattern shift. Our experiments demonstrate that the shift in the shape oscillation pattern in regenerating Hydra tissue pieces is caused by the formation of a functional mouth and not by shape symmetry breaking as previously assumed. Thus, model assumptions must be revised in light of these new experimental data, which can be used to constrain and validate improved theoretical models of pattern formation in Hydra.